DESCRIPTION (provided by candidate): The goal of this application is to provide a supervised training program that will promote the candidate's development into an independent physician - scientist. This will be accomplished through a coordinated effort in the Department of Otolaryngology and the Interdisciplinary Stem Cell Institute (ISCI), at University of Miami. This proposal will enable the candidate to pursue his interest in mechanisms of regeneration in the olfactory system through a mentored plan to study nasal stem cells and specific signaling pathways. Research Program: Although olfactory neurons in the nose are replaced continually from progenitor or stem cells, certain conditions can lead to a loss of olfactory function that likly is a consequence of failures in this repair process. Anosmia can occur following head injury, prior upper respiratory infections, active sinusitis, or as a consequence of the aging process. There are currently no effective treatments for sensorineural anosmia. The broad, long term goals of this proposal are to develop novel treatments for anosmia. Our interest in determining mechanisms regulating olfactory progenitors has led to the novel finding that olfactory cells expressing the c-kit receptor can give rise to olfactory neurons. The central hypothesis of this proposal is that c-kit (+) progenitor cells serve a key role in adult olfactory maintenance. The experiments proposed here will directly define the role of nasal c-kit (+) progenitors in olfactory neurogenesis and regeneration under various conditions. Defining the function of specific nasal stem and progenitor cells underlying olfactory neuronal replacement, and determining their regulatory mechanisms, are essential steps towards the establishment of new treatments for anosmia. Training Program: The candidate will participate in a didactic program to enhance his career development. Courses and seminars at University of Miami relating to ethics, research design, and biostatistics will be audited. Also, he will participate in intellectual activities in he Otolaryngology Department and the Stem Cell Institute. Frequent meetings with advisors will be utilized to monitor progress. Dr. Josh Hare, ISCI Director, and Dr. Nirupa Chaudhari, Professor of Physiology and Biophysics, will serve as Mentors.